Fig. 2: The RANKL-RANK signaling functioning model that is suggested controls osteoblast differentiation and bone formation in inflammatory conditions in AxSpA.

BM-MSCs provide a crucial job in normal joints by maintaining bone homeostasis and repairing damaged lesions due to their distinct normal environment activities. However, selective RANKL expression in MSCs may contribute to joint inflammation in an inflammatory environment. MSCs are thus candidate target cells for TNF in these disorders. Different cells secreting IL-22 in entheses provide an additional option for the involvement of BM-MSCs in AxSpA. The majority of studies evaluating the function of BM-MSCs in the pathophysiology of AxSpA have focused on their engagement in the ossification of entheses, which is characteristic of persistent AxSpA. In inflammatory MSCs expressing RANK, RANKL binding to RANK stimulates RANKL to reverse signaling in osteoblasts and promotes osteoblast differentiation⁵⁷.